Heme oxygenase-1 (HO-1) catalyzes the first step in the degradation of heme. HO-1 cleaves the α-meso carbon bridge of b-type heme molecules by oxidation to yield equimolar quantities of biliverdin IXa, carbon monoxide (CO), and free iron. Subsequently, biliverdin is converted to bilirubin via biliverdin reductase, and the free iron is sequestered into ferritin (the production of which is induced by the free iron).
CO is recognized as an important signaling molecule (Verma et al., Science 259:381-384, 1993). It has been suggested that carbon monoxide acts as a neuronal messenger molecule in the brain (Id.) and as a neuro-endocrine modulator in the hypothalamus (Pozzoli et al., Endocrinology 735:2314-2317, 1994). Like nitric oxide, CO is a smooth muscle relaxant (Utz et al., Biochem Pharmacol. 47:195-201, 1991; Christodoulides et al., Circulation 97:2306-9, 1995) and inhibits platelet aggregation (Mansouri et al., Thromb Haemost. 48:286-8, 1982). Inhalation of low levels of CO has been shown to have anti-inflammatory effects in some models.
Intimal hyperplasia, a thickening of the inner layer of the blood vessel, is a pathological process that arises from vascular injury subsequent to procedures such as angioplasty, bypass surgery or organ transplantation. Intimal hyperplasia continues to limit the success of these therapeutic interventions.